Ocular surface diseases affecting the corneal and conjunctival epithelia and immediately subjacent tissues are among the most difficult external eye diseases to treat. The overall goals of this grant are improve our understanding of the normal and diseased conjunctiva with the eventual aim being to define and manipulate some of the factors responsible for ocular surface disease. Hyperproliferation of the conjunctival epithelium has been demonstrated in ocular surface diseases such as ocular cicatricial pemphigoid (OCP) and vitamin A deficiency. It is unknown whether this is a general response of the tissue to inflammation or specific to disease. Therefore, one of the aims of this application is to investigate the role of inflammation in differentiation of the ocular surface using both animal models and patients. Ocular surface diseases are frequently associated with conjunctival scarring and subepithelial fibrosis; however, little attention has been paid to the biology of the conjunctival subepithelial cells and matrix. In this study, we will study conjunctival fibrocytes in culture, concentrating both on their growth characteristics and on the production of collagen and glycosaminoglycans by these cells from normal and diseased eyes. Furthermore, we will assess the subepithelial matrix and cells immunohistochemically in tissue from normal and diseased eyes. Conjunctival biopsy and impression cytology are two methods of obtaining samples of conjunctiva for analysis. Impression cytology is less invasive than conjunctival biopsy, but may not provide as much information. By comparing these methods with respect to goblet cell frequency, mitotic rate, and squamous metaplasia, we propose to determine whether it is possible to use impression cytology rather than conjunctival biopsy to define types of ocular surface disease. Finally, we will measure the effect of systemic cytotoxic immunosuppression on several defined characteristics of OCP to determine the response to therapy.